Watching Alzheimer’s
How to image brain plaques

Context: The sticky plaques characteristic of Alzheimer’s disease build up in the brains of patients well before cognitive symptoms appear. But the most reliable noninvasive method for detecting these plaques – positron emission tomography (PET) – is prohibitively expensive and unwieldy, requiring hard-to-handle, short-lived radioactive materials. Now, two groups of researchers have demonstrated more-practical methods for monitoring the plaque development characteristic of Alzheimer’s disease. One of them promises higher-resolution images than PET.

Methods and Results: Conventional imaging chemicals do not work well with amyloid plaques because the brain is separated from potentially toxic chemicals in the blood by the blood-brain barrier; nor can the typically water-loving chemicals readily access the fatty plaques. Martin Hintersteiner of the Novartis Institutes of Biomedical Research in Basel, Switzerland, found a dye that crosses the blood-brain barrier in mice and binds to plaques. In a procedure called near-infrared imaging, the dye yields a quantitatively stronger signal as the number of plaques in the brain increases. In a separate study, Makoto Higuchi and colleagues at Riken Brain Science Institute and Dojin Laboratories in Japan found another dye that works in conjunction with magnetic-resonance imaging, a technique common in both research and the treatment of patients. The resulting images correlated well with images of the same mice obtained after staining slices of their brains.

Why It Matters: Usually, researchers studying Alzheimer’s must dissect animal brains to see the effects of treatments. But monitoring a living brain over time would yield much more useful information and might even help in early diagnosis. Because Hintersteiner’s and Higuchi’s imaging techniques cost as little as a fiftieth as much as PET, and because the chemicals are easier to work with, live experiments once considered out of reach can now be performed on animals – and, with the MRI technique, potentially even people.

Sources: Higuchi, M., et al. 2005. 19F and 1H MRI detection of amyloid ß plaques in vivo. Nature Neuroscience 8:527-33.
Hintersteiner, M., et al. 2005. In vivo detection of amyloid-ß deposits by near-infrared imaging using an oxazine-derivative probe. Nature Biotechnology 23:577-83.